Osteoactivin inhibition of osteoclastogenesis is mediated through CD44-ERK signaling
Experimental & Molecular Medicine
;
: e257-2016.
Article
in English
| WPRIM
| ID: wpr-117333
ABSTRACT
Osteoactivin is a heavily glycosylated protein shown to have a role in bone remodeling. Previous studies from our lab have shown that mutation in Osteoactivin enhances osteoclast differentiation but inhibits their function. To date, a classical receptor and a signaling pathway for Osteoactivin-mediated osteoclast inhibition has not yet been characterized. In this study, we examined the role of Osteoactivin treatment on osteoclastogenesis using bone marrow-derived osteoclast progenitor cells and identify a signaling pathway relating to Osteoactivin function. We reveal that recombinant Osteoactivin treatment inhibited osteoclast differentiation in a dose-dependent manner shown by qPCR, TRAP staining, activity and count. Using several approaches, we show that Osteoactivin binds CD44 in osteoclasts. Furthermore, recombinant Osteoactivin treatment inhibited ERK phosphorylation in a CD44-dependent manner. Finally, we examined the role of Osteoactivin on receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteolysis in vivo. Our data indicate that recombinant Osteoactivin inhibits RANKL-induced osteolysis in vivo and this effect is CD44-dependent. Overall, our data indicate that Osteoactivin is a negative regulator of osteoclastogenesis in vitro and in vivo and that this process is regulated through CD44 and ERK activation.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Osteoclasts
/
Osteolysis
/
Phosphorylation
/
Stem Cells
/
In Vitro Techniques
/
Bone Remodeling
Type of study:
Prognostic study
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2016
Type:
Article
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